Research Program Area: Health & Exposure
Topic Areas: Health Effects of Air Pollution
The previously unknown metabolic fate of nitrate and nitrite introduced into the respiratory tract has been studied because they exist in the ambient California urban aerosol or can be derived from known nitrogenous air pollutants. The metabolic fate of NO, ions in the digestive tract also has been studied for comparative purposes because these ions are known to form cancer-causing nitrosamines therein under super-ambient exposure conditions. Radiochemical syntheses (Section 3.2) for 0.5 Ci quantities of radioactive nitrogen-13 (half-life = 10 min) labeled NO, tracer ions have been developed to address the objectives of this study. This has permitted the fate of these ions to be studied at pharmacologically non-perturbing concentrations which may more accurately reflect their biological fate under realistic ambient exposure conditions. The development and evaluation of first-generation radiochromatographic methods for chemical analysis of N-13 labeled compounds in biological fluids are described (Section 3.2). The organ distribution of N-13 has been measured following intratracheal, gavage, and intravenous administration to adult mice and rabbits and to pregnant mice. The tracer NO, ions were in the chemical form of nitrate and nitrite (no added carrier) (Section 3.3). The N-13 label from both nitrate and nitrite was rapidly cleared from the organ of introduction and distributed throughout the body. An equilibrium distribution was reached in about 5 minutes after injection and did not change over the next 30 minutes. Less than 3% of the tracer was excreted rapidly into the urine. The label from both nitrate and nitrite crossed the placenta to the fetus. Both nitrate and nitrite were found to react in vivo, but the conversion of nitrite was much more extensive than for nitrate. These pharmacokinetic results suggested a need for additional work. The overall results suggest that the toxicological databases for inhaled nitrogen dioxide gas, a precursor to nitrate and nitrite, and ingested inorganic nitrates and nitrites are useful in evaluating the health hazard associated with air pollutant inorganic nitrates. A biochemical mechanism is postulated for pathogenic effects associated with exposure to compounds containing nitrogen in its higher oxidation states.
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